Radiation therapy involves the use of high-energy waves or streams, commonly referred to as radiation, that induce ionization in tissue for the treatment of disease. Radiation therapy may be referred to by such terms a radiotherapy, x-ray therapy, gamma-ray therapy, beta-ray therapy, charged-particle therapy, or irradiation.
One disease commonly treated using radiation therapy is cancer. Cancer is a cellular disease where abnormal cells, commonly referred to as cancer cells, grow and divide more rapidly than the normal cells around them. In radiation therapy, therapy equipment aims specific amounts of radiation at these cells, e.g., tumors or areas of the body. Radiation in therapeutic doses kills cancer and intrinsic vascular cells, thus preventing them from growing and dividing.
Radiation administered during radiation therapy not only acts on the cancer cells, but it also acts on proximate normal cells. To limit the effect of radiation on normal cells, doctors carefully limit the doses of radiation and spread the treatments out over time. Additionally, shielding of normal cells is also used. Even with these precautions, an organ having cancer cells therein wherein the cancer cells are being treated by radiation may have proximate normal cells in the organ damaged. Additionally, normal cells in other organs may be damaged. For example, treatment of a nasal cancer might adversely affect normal cells in an eye.
In a number of cases, normal cells damaged during radiation therapy will recover, but in some cases, they will not. One complication of radiation treatment is radiation-induced vasculopathy. Some radiation therapies that may cause radiation-induced vasculopathy include plaque brachytherapy, external beam irradiation, or proton beam.
In ophthalmic plaque brachytherapy, a plaque, which is a small generally metallic object containing radioisotopes (e.g., radioactive seeds), is surgically implanted on the exterior of the eye. The plaque is typically sutured to the outside wall of the eye (i.e., the sclera) proximate an intraocular melanoma (a type of cancer) located therein. The radioisotope associated with the plaque emits radiation that penetrates the sclera and treats the melanoma. Generally, the plaque provides shielding so that proximate organs, and thus the normal cells therein, are protected from the radiation, at least to some degree. The plaque generally remains on the eye until the intraocular melanoma has received a therapeutic dose of radiation (e.g., enough to destroy it). The plaque is then surgically removed.
Intraocular melanomas are classified into three general categories based on size. In accordance with the American Joint Committee on Cancer (AJCC) and COMS Staging Criteria, intraocular melanomas up to 2.4 millimeters in height and less than 10 mm in width are classified as T1 or small. Intraocular melanomas that are more than 2.4 to 9.9 millimeters in height and less than 16 mm in width are considered T2 or medium. Those intraocular melanomas that are 10 mm or larger in height and/or 16 mm or larger in width are T3 or COMS-large.
As the size of the intraorgan cancers, such as intraocular melanomas, increases, the amount of radiation required to treat them effectively also increases. Unfortunately, as the radiation level is increased, the probability of irreversible damage to otherwise normal cells increases. More specifically, the incidental damage to normal cells may not be reversible, in whole or in part, or the damage may cause other problems. Thus, in some cases, the organ might be saved, but the functionality of that organ may be severely affected. In other cases, the effect could lead to a loss of the function of the organ (e.g., in the case of an eye, blindness).
Two types of radiation-induced vasculopathy occurring in the eye from radiation therapy, on either the eye or an adjacent organ, are retinopathy and neuropathy. These two conditions are common sight-limiting complications of ophthalmic radiation therapy. Radiation retinopathy is associated with the eye's retina. Where it involves the macula (i.e., radiation maculopathy), blindness is a significant risk. Radiation neuropathy is generally associated with the eye's optic nerve, and for patients with this condition blindness is also a significant risk.
The risk of radiation-induced vasculopathy is a function of the effective dose of radiation required to treat the cancer, the pre-existing presence of systemic disease such as diabetes, and the use of radiation sensitizers (i.e., pre-treatments such as chemotherapy designed to increase the effectiveness of the radiation therapy).
Radiation retinopathy, which may present with the symptoms of loss of visual acuity or visual disturbance, includes such damage as obliterative endarteritis (endothelial cell loss and thickened vessel walls) and intraretinal microangiopathy. This damage (or side effect) presents as tissue ischemia caused by undesirable conditions such as vascular occlusions, capillary dropout and leakage (hemorrhages, exudation and edema) and microaneurysms. If any of these undesirable conditions is left untreated, the undesirable condition may worsen and/or cause other undesirable conditions, such as neovascularization, that ultimately lead to a loss of visual acuity and/or visual disturbance. While some of these undesirable conditions are controllable using laser photocoagulation, not all are. In particular, where these undesirable conditions occur because of treatment of subfoveal and macular choroidal melanomas in the eye, they are not amenable to or controllable by laser techniques.
Radiation-induced optic neuropathy (RON), while uncommon, often results in blindness. Posterior RON occurs on the posterior of the eye, thus its pathophysiologic events are hidden. Posterior RON is typically associated with external beam irradiation. Anterior RON occurs on the anterior of the eye (i.e., visible by looking through the eye's lens). Anterior RON is typically associated with ophthalmic plaque or proton beam irradiation.
Posterior RON typically presents with the symptom of loss of visual acuity, while anterior RON typically presents with the symptom of visual disturbance, such as “central haze.” In patients with anterior RON, ophthalmic examination reveals optic disc microangiopathy, edema, hemorrhage, neovascularization. Additionally, radiation retinopathy may also be present.
RON is also classified as early or late. In the case of early RON, it occurs within several weeks of irradiation and is characterized by acute inflammation leading to optic nerve pallor. Late RON occurs years after treatment and is characterized by vasculitis, necrosis, and optic disc pallor, all of which are generally irreversible.
What is needed in the art is a treatment for radiation-induced vasculopathy to stabilize, or regress, the undesirable conditions of radiation therapy on organs, so that larger cancers, where these undesirable conditions pose a more significant risk as to overall organ function, can be treated effectively such that a functioning organ, at least to some degree, is preserved.